Pharm - Antiepileptic Drugs (Aed)

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ASD/AED
goals

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depress synaptic transmission and dec. nerve conduction
limit propagation
elevate threshold of stimuli

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Classification of Epilepsies
Partial seizures

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discrete focus
one hemisphere
can generalize

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Classification of Epilepsies
Partial seizures
simple partial

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Jacksonian
does not spread
no alteration of consciencousness
20-60 sec
m. contractions and hall

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Classification of Epilepsies
Partial seizures
complex partial

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local discharge which becomes more widespread with alteration of consciousness
most common
automatism/hall

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Classification of Epilepsies
Generalized seizures

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both hemispheres with rapid spread

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Classification of Epilepsies
Generalized seizures
tonic-clonic (grand mal)

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most common generalized
bilat movement that begin suddenly
abrupt loss of consciousness
tonic contractions for 10-20 sec; followed by relaxation
amnesea

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Classification of Epilepsies
Generalized seizures
absence
petit mal

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sudden onset and offset
non-convulsive 10 sec

alteration of consciousness and cessation of ongoing activity
childhood - ADHD diag.
up too 100/day

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Classification of Epilepsies
Generalized seizures
Myoclonic

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rare
non-convulsive, sudeen
lightening like jerks
no alteration of consciousness
can become tonic clonic

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Classification of Epilepsies
Generalized seizures
Atonic

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children
sudden loss of m. tone
head drops; wear helmets b.c of frequent falls

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Classification of Epilepsies
Generalized seizures
tonic clonic
treatment

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Carbamazepine
Phenytoin

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Classification of Epilepsies
Generalized seizures
absence
treatment

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Ethosuximide
Valproic acid

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Classification of Epilepsies
Generalized seizures
atonic
treatment

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valproic acid

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Classification of Epilepsies
partial seizures
Complex partial
treatment

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Carbamazepine
Phenytoin

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Classification of Epilepsies
Febrile seizures
treatment

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typically do not require medication
Phenobarbitol

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Classification of Epilepsies
Status Epilepticus
treatment

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IV Diazepam or lorazepam
IV fosphenytoin or phenobarbital

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Classification of Epilepsies
Febrile seizures

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kids up to 5 yrs
2-4% of kids
generalized tonic clonic of short duration

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Classification of Epilepsies
Status Epilepticus

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prolonged >20 min of any type
tonic clonic is life threatening

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AED General Side E
Females

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decrease oral contraceptive
adverse fetal abnormalities
folic acid supp. helps
Vit K def. in newborns

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Drugs
Phenytoin
Fosphenytoin
Indications

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status epileticus
partial seizures
tonic clonic

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Drugs
Phenytoin
Fosphenytoin
Mech

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block Na channels in inactive state; prolong refractory period

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Drugs
Phenytoin
Fosphenytoin
Pharmaco

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slowly absorbed; slow on and long duration
maintence therapy
rate of ab very different for diff patients (35-95%); don't change brands

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Drugs
Phenytoin
Metab

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liver enz. saturates at high doses so zero order kinetics
half life 7-42 hrs
low TI, monitor plasma level

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Drugs
Phenytoin
Fosphenytoin
Adverse Effects (Impt.)
common

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N&V; visual (early)
ataxia
confusion
gingival hyperplasia - benign
hirsutism - facial hair

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Drugs
Phenytoin
Fosphenytoin
Adverse Effects (Impt.)

Rare

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megoblastic anemia
coarsening of facial features - kids (bone and collagen growth)
rashes and blood dyscrasias
fetal malformation - fetal-hydantoin syndrome
Osteomalacia

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Drugs
Phenytoin
Interactions

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inc. metab of oral contraceptives and coagulants;
inc metab of cabam and VA
Carbamazepine and phenobarbital inc metab of phenytoin
VA and Cimetidine dec metab of phenytoin

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Drugs
Carbamazepine
Oxcarbazepine
Indications

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partial and tonic-clonic

also trigeminal neuralgia
also biploar disease

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Drugs
Carbamazepine
Oxcarbazepine
Mech

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block Na channels in inactive state
prolong cell refract

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Drugs
Carbamazepine
Oxcarbazepine
Adverse
Common

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N&V
visual
Ataxia
Sedation at high doses

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Drugs
Carbamazepine
Oxcarbazepine
Adverse
Rare

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hyponatremia with water retention
idiosyncratic rxn: rashes and blood dyscrasis

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Drugs
Carbamazepine
Oxcarbazepine
Interactions

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autometabolism
Inc metab of other anticonvulsants and oral contraceptives
Cimetidine dec metab

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Drugs
Valproic Acid
Indications

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absence
myoclonic
atonic

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Drugs
Valproic Acid
Adverse
Common

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N&V
heart burn
wt gain
hair loss - temporary
ataxia
tremor!!

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Drugs
Valproic Acid
Adverse
Rare

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fetal malformations - spina bifida
idiosyncratic hepatoxicity
polycystic ovarian syndrome

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Drugs
Valproic Acid
Interactions

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inhib metab of carbamazeoine and phenytoin

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Drugs
Ethosuximide
Indications

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Absence

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Drugs
Ethosuximide
Mech

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reduces low threshold T-type Ca current that provides pacemaker activity in thalamus

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Drugs
Ethosuximide
Adverse effects

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N&V and fatigue

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Drugs
Ethosuximide
Adverse
Rare

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rashes and blood dyscrasias

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Drugs
Phenobarbital
Indications

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febrile seizures in infants
status epilepticus

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Drugs
Phenobarbital
Mech

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GABA mediated inhibition of neuronal activity

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Drugs
Phenobarbital
Adverse Effects

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paradoxical hyperactivity and shrotened attention span
sedation and nystagmus with chronic use
seizure if abruptly discontinued

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Drugs
Phenobarbital
Chronic use

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induction of metab of other microenzymes

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Drugs
Diazepam
Lorazepam
INdications

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status epilepticus

it's a benzo!

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Drugs
Diazepam
Lorazepam
Mech

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GABA mediated inhibitions of neuronal
rapid onset/ short acting (30-45min)
rapid tolerance

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Drugs
Diazepam
Lorazepam
Adverse Effects

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rapid development of tolerance limits chronic use
sedation and paradoxical hyperactivity

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Drugs
Diazepam
Lorazepam
Adverse Effects

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rapid development of tolerance
sedation and paradoxical hyperactivyt limit use

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Newer AEDs
Lamotrigene
Mech

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voltage and use dependent Na channel blockade

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Newer AEDs
Lamotrigene
Adverse Effects

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dizziness
headache
diplopia
nausea
S-J syndrome and toxic epidermal necoriss in kids

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Newer AEDs
Lamotrigene
Pharmaco/Interactions

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half life reduced by 50% by inducing agents phenytoin an dcarbamazepine.
valproic acid inhibits clearance